Enhanced stereoselectivity in internucleotidic bond formation by the use of the chiral ribose moiety of thymidine

This paper deals with the synthesis of new cyclic thymidine 3'-phosphoramidite building blocks having a covalent linker between the trityl type 5'-hydroxyl protecting group and the phosphorus atom attached to the 3'-hydroxyl group of thymidine. The ring structures were designed to reduce the conformational freedom around the phosphorus center so that the stereoselectivity in the internucleotide linkage formation would be improved. The linkers were also designed to be removed readily by treatment with aqueous ammonia. These building blocks were synthesized in good yield by one-pot cyclization of the diol precursors with dichloro(N,N-diisopropylamino)phosphine, despite their large-membered ring. Various activators having 1H-tetrazole, imidazole, and triazole structures were investigated to find the best selectivity in the synthesis of thymidylyl(5'-3')thymidine phosphorothioate. It turned out that our cyclic phosphoramidites gave preferentially the R(p) diastereoisomer in high coupling yield applicable to the solid-phase synthesis of oligodeoxynucleotides. It should be noted that high stereoselectivity was achieved without any chiral sources other than the 2'-deoxyribose moiety itself. The mechanistic studies revealed the importance of the steric bulk and the acidity of the activators. It was also found that the steric bulk of the alcoholic nucleophile was an important factor that determined the stereoselectivity in our systems.     

Subordination to periodic processes and synchronization

We study the subordination to a process that is periodic in the natural time scale, and equivalent to a clock with N states. The rationale for this investigation is given by a set of many interacting clocks with N states. The natural time scale representation corresponds to the dynamics of an individual clock with no interaction with the other clocks of this set. We argue that the cooperation among the clocks of this set has the effect of generating a global clock, whose times of sojourn in each of its N states are described by a distribution density with an inverse power law form and power index μ<2. This is equivalent to extending the widely used subordination method from fluctuation-dissipation processes to periodic processes, thereby raising the question of whether special conditions exist of perfect synchronization, signaled by regular oscillations, and especially by oscillations with no damping. We study first the case of a Poisson subordination function. We show that in spite of the random nature of the subordination method the procedure has the effect of creating damped oscillations, whose damping vanishes in the limiting case of N?1, thereby suggesting a condition of perfect synchronization in this limit. The Bateman’s mathematical arguments [H. Bateman, Higher Transcendental Functions, vol. III, Robert K Krieger, Publishing Company, Inc. Krim.Fr. Drive Malabar, FL; Copyright 1953 by McGraw-Hill Book Company Inc.] indicate that the condition of perfect synchronization is possible also in the non-Poisson case, with μ<2, although it may lie beyond the range of computer simulation. To make the theoretical predictions accessible to numerical simulation, we use a subordination function whose survival probability is a Mittag-Leffler exponential function. This method prevents us from directly establishing the macroscopic coherence emerging from μ=2, which generates a perfect form of 1/f noise. However, it affords indirect evidence that perfect synchronization signaled by undamped regular oscillations may be produced in this case. Furthermore, we explore a condition characterized by an excellent agreement between theory and numerical simulation, where the long-time region relaxation, with a perfect inverse power law decay, emerging from the subordination to ordinary fluctuation-dissipation processes, is replaced by exponentially damped regular oscillations.     

Neutrino astrophysics and SN 1987 A(*)(**)

Summary In this paper we summarize the Mont Blanc observation of the Large Magellanic Cloud supernova, exploded on February 23, 1987. The problem of two bursts, recorded in different underground detectors and separated in time by 4.7 hours, is also discussed. Since the different observations are not contradictory from the experimental point of view, some changements are required in the current predictions of the theoretical models of a gravitational stellar collapse in order to fit all the experimental data. Finally, the combined analysis of the data, recorded in all the neutrino and gravitational wave detectors running at the time of the supernova, clearly indicates a long duration of the phenomenon. Thus, any serious (even if difficult) tentative to explain how a star ends its life as a supernova should be based on all the experimental data available, recorded in different, independent experiments running at intercontinental distances at the time of supernova 1987 A. To speed up publication, the proofs were not sent to the authors and were supervised by the Scientific Committee.     

Effects on generalized growth models driven by a non-Poissonian dichotomic noise

In this paper we consider a general growth model with stochastic growth rate modelled via a symmetric non-poissonian dichotomic noise. We find an exact analytical solution for its probability distribution. We consider the, as yet, unexplored case where the deterministic growth rate is perturbed by a dichotomic noise characterized by a waiting time distribution in the two state that is a power law with power 1 < μ < 2. We apply the results to two well-known growth models; Malthus-Verhulst and Gompertz.     

Low Temperature Aqueous Living/Controlled (RAFT) Polymerization of Carboxybetaine Methacrylamide up to High Molecular Weights

Among the class of zwitterionic polymers poly(carboxybetaine)s (poly(CB)s) are unique, emerging as the only ultra‐low fouling materials known allowing the preparation of biosensors, fouling resistant nanoparticles, and non‐adhesive surfaces for bacteria. Poly(carboxybetaine methacrylate) and poly(carboxybetaine acrylamide) have been prepared via atom transfer radical polymerization (ATRP), however a polymerization with living characteristics has not been achieved yet. Herein, the first successful living/controlled reversible addition fragmentation transfer (RAFT) polymerization of (3‐methacryloylamino‐propyl)‐(2‐carboxy‐ethyl)‐dimethyl‐ammonium (carboxybetaine methacrylamide) (CBMAA‐3) in acetate buffer (pH 5.2) at 70 and 37 °C is reported. The polymerization afforded very high molecular weight polymers (determined by absolute size exclusion chromatography, close to 250 000 g · mol⁻¹ in less than 6 h) with low PDI (<1.3) at 70 °C. The polymerization was additionally carried out at 37 °C allowing to achieve yet lower PDIs (1.06 ≤ PDI ≤ 1.15) even at 90% conversion, demonstrating the suitability of the polymerization conditions for bioconjugate grafting. The living character of the polymerization is additionally evidenced by chain extending poly(CBMAA‐3) at 70 and 37 °C. Block copolymerization from biologically relevant poly[N‐(2‐hydroxypropyl)methacrylamide] macroCTAs was additionally performed.